Nicole Olivier, Hadzibegovic Senka, Gajda Judyta, Bontempi Bruno, Bem Tiaza, Meyrand Pierre
Institut des Maladies Neurodégénératives, Université de Bordeaux, UMR 5293, 33000 Bordeaux, France.
CNRS, Institut des Maladies Neurodégénératives, UMR 5293, 33000 Bordeaux, France.
Sci Rep. 2016 Mar 7;6:22728. doi: 10.1038/srep22728.
Post-learning hippocampal sharp wave-ripples (SWRs) generated during slow wave sleep are thought to play a crucial role in memory formation. While in Alzheimer's disease, abnormal hippocampal oscillations have been reported, the functional contribution of SWRs to the typically observed spatial memory impairments remains unclear. These impairments have been related to degenerative synaptic changes produced by soluble amyloid beta oligomers (Aβos) which, surprisingly, seem to spare the SWR dynamics during routine behavior. To unravel a potential effect of Aβos on SWRs in cognitively-challenged animals, we submitted vehicle- and Aβo-injected mice to spatial recognition memory testing. While capable of forming short-term recognition memory, Aβ mice exhibited faster forgetting, suggesting successful encoding but an inability to adequately stabilize and/or retrieve previously acquired information. Without prior cognitive requirements, similar properties of SWRs were observed in both groups. In contrast, when cognitively challenged, the post-encoding and -recognition peaks in SWR occurrence observed in controls were abolished in Aβ mice, indicating impaired hippocampal processing of spatial information. These results point to a crucial involvement of SWRs in spatial memory formation and identify the Aβ-induced impairment in SWRs dynamics as a disruptive mechanism responsible for the spatial memory deficits associated with Alzheimer's disease.
慢波睡眠期间产生的学习后海马尖波涟漪（SWRs）被认为在记忆形成中起关键作用。虽然在阿尔茨海默病中已报道有异常的海马振荡，但SWRs对典型观察到的空间记忆损害的功能贡献仍不清楚。这些损害与可溶性淀粉样β寡聚体（Aβos）产生的退行性突触变化有关，令人惊讶的是，在日常行为中，Aβos似乎未影响SWRs动态。为了阐明Aβos对认知挑战动物SWRs的潜在影响，我们对注射了载体和Aβo的小鼠进行了空间识别记忆测试。虽然Aβ小鼠能够形成短期识别记忆，但遗忘速度更快，这表明它们成功编码了信息，但无法充分稳定和/或检索先前获取的信息。在没有先前认知要求的情况下，两组小鼠的SWRs具有相似的特性。相反，当面临认知挑战时，Aβ小鼠中未观察到对照组中出现的编码后和识别后SWRs峰值，这表明海马对空间信息的处理受损。这些结果表明SWRs在空间记忆形成中起关键作用，并确定Aβ诱导的SWRs动态损害是导致与阿尔茨海默病相关的空间记忆缺陷的破坏机制。
